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Isolation and characterization of a soluble antigen complex of Plasmodium falciparum with pyrogenic properties.

A soluble antigen complex, previously designated antigen no. 7 (Ag7) on the basis of the pattern obtained by crossed immunoelectrophoresis of culture supernatants of P. falciparum, was isolated by affinity chromatography. It was shown to be synthesized at the schizont stage of the parasite growth cycle and to be located on the surface of the schizonts. Antibodies to Ag7 did not inhibit the growth of the parasite in vitro. Ag7 is recognized by immune human sera from many parts of the world and it stimulated the production of specific antibody in mice when incorporated into immune-stimulating complex (ISCOM) structures. It also specifically stimulated in vitro proliferation of lymphocytes from clinically immune adults. That it induced the secretion of interleukin 1 by human monocytes and was pyrogenic in rabbits was of particular interest. Thus Ag7 has endotoxin-like properties which make it a possible candidate for an antitoxic malaria vaccine.

Animals↗

[The effect of pyrogens on the ultrastructure of the reticular nuclei and large raphe nucleus of the medulla oblongata in the cat].

Investigation of ultrastructure of reticular nuclei in the large nucleus of the raphe medullae oblongatae has revealed a close position of some neurons to the vascular endothelium. Intravenous administration of exo- or endogenic pyrogens produces dilatation of the perivascular space and appearance of lipid phagocytes in it. Simultaneously in neurons, glio- and endotheliocytes lysosomes, lipofuscin and vacuoles are revealed. The changes detected are transitory and not specific for the agents applied.

Animals↗

Effects of sodium salicylate on the febrile response and increased levels of cyclic AMP in cerebrospinal fluid during endogenous pyrogen-induced fever in rabbits.

To further evaluate the causality between endogenous pyrogen (EP)-induced fever and cyclic adenosine-3',5'-monophosphate (cyclic AMP) level, the effects of sodium salicylate (SS) on the febrile response and increased levels of cyclic AMP in both cerebrospinal fluid (c.s.f.) and plasma during EP-induced fever in rabbits were observed. The results suggest that cyclic AMP is probably involved in the central mediation of EP-induced fever and that increased concentration of cyclic AMP in c.s.f. associated with EP-induced fever is not the result of temperature elevation but appears to be caused by the increased synthesis in the central nervous system. In addition it is confirmed that blood is impossibly a contributory source of increased cyclic AMP in c.s.f. during EP fever, and that SS may act subsequent to the increase in cyclic AMP.

Animals↗

Effect of endogenous pyrogen, corticosteroids and inhibitors of prostaglandins and leukotrienes on the plasma concentrations of haptoglobin and fibrinogen in rats.

Injections of endogenous pyrogen (EP) in normal rats significantly increased plasma concentration of haptoglobin and fibrinogen while in adrenalectomized animals the same treatment was ineffective. Nevertheless when cortisone was injected simultaneously with EP into adrenalectomized rats the responses of fibrinogen and haptoglobin were restored. These results suggest that biosynthesis of fibrinogen and haptoglobin is corticosteroid-dependent. Inhibition of the cyclo-oxygenase pathway with ibuprofen or the lipoxygenase pathway with BW755C had no effect on the increase of plasma fibrinogen or haptoglobin levels stimulated by either EP or endotoxin. These data indicate that neither prostaglandins nor leukotrienes are involved in the production of these acute phase reactants induced by either stimulus.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Easy production of sterile, pyrogen-free dialysate.

Hemodialysis (HD) hypotension is frequently encountered during conventional acetate HD. Recently it has been suggested that monocytes that adhere to the dialysis membrane are also stimulated by endotoxins diffusing from the dialysate side. Stimulated monocytes, however, release interleukin-1, which mediates fever and hypotension through its action on the cyclo-oxygenase cascade. To prevent this endotoxin-induced stimulation of monocytes, a hemofilter with a polyamide membrane (FH 88, Gambro, Lund, Sweden, cut-off 20,000 daltons, surface area 2.0 m2) was interposed between the dialysate outlet of the HD machine and the dialyzer. The data obtained clearly show that the filtered dialysate was always pyrogen-free when tested with a limulus-amebocyte-lysate assay. In addition, in 80% of cases no bacteria were detected after the sterilizing filter. Almost no febrile episodes were observed when sterile dialysate was used.

Biological Assay↗

[Effect of leukocyte pyrogen on the phagocytic properties of macrophages in tissue culture].

The effect of rabbit leukocytic pyrogen (LP) on the phagocytic activity of the peritoneal macrophages of albino mice against shigellae was investigated. The dose-effect dependence was revealed: high LP doses depressed the phagocytosis, and low ones were insufficiently effective; addition of average LP doses against the kanamycin background stimulated both the absorption phase and that of shigella digestion. Phagocytosis stimulation with LP was also accompanied by an increase of the acid phosphatase lysosomal enzyme activity in macrophages; the RNA content was not changed.

Acid Phosphatase↗

Effect of protein synthesis inhibitors on leukocytic pyrogen-induced in vitro hypothalamic prostaglandin production.

In order to study the antipyretic effect of inhibitors of protein synthesis, hypothalamic tissue was incubated in vitro under controlled conditions and the amount of prostaglandin E2 (PGE2) measured in the supernatant medium. Rabbit anterior hypothalamic tissue was incubated with purified human leukocytic pyrogen (LP) and after 60 minutes the supernatant fluid was assayed for PGE2 by radioimmunoassay. Control tissue incubated with Eagle's medium (MEM) released elevated levels of PGE2; however, the addition of polymyxin B (PmxB), a cationic antibiotic which blocks the activities of bacterial endotoxins, significantly reduced PGE2. In addition, endotoxin added to MEM induced from the brain tissue PGE2 production which could be reduced by the addition of PmxB. Thus, commercial culture media such as MEM may contain sufficient amounts of endotoxin to stimulate brain PGE2 production in vitro. Purified human LP incubated with hypothalamic tissue in the presence of PmxB induced PGE2 production in a dose-dependent fashion. This release could be reduced (p less than 0.001) by the presence of either cycloheximide or puromycin during incubation with LP. The addition of these inhibitors to unstimulated hypothalamic tissue incubations did not reduce background levels of PGE2. It is concluded that the antipyretic effect of protein synthesis inhibitors results in a specific decrease in LP-induced levels of PGE2.

Animals↗

Increased production of endogenous pyrogen and lysozyme by blood monocytes in sarcoidosis.

Blood monocytes from patients with sarcoidosis were incubated in vitro, and secretion of endogenous pyrogen (EP), the protein which mediates fever, and lysozyme (L) were measured. After incubation with endotoxin, monocytes from 5 patients with sarcoidosis released twice as much EP as did monocytes from normal individuals (p < .001). Initial 24-hr secretion of L by monocytes from 6 of 11 additional patients with sarcoidosis exceeded the normal range of values for cells from 11 age- and sex-matched control individuals. Cells with initially augmented secretion rates continued to secrete increased amounts of L for 3 days. A correlation was noted between in vitro secretion of L by monocytes and serum levels of L in the same patient. These studies indicate that circulating mononuclear cells in some patients with sarcoidosis have an increased capacity to secrete EP and/or L prior to tissue localization.

Adolescent↗

The effect of pyrogen induced fever on pharmacokinetics of rifamycin SV.

The fever was evoked in rabbits by single iv injection of pyrogen-standard from E. coli, and rifamycin SV was administered at the peak of the fever (T = 1.7 degrees C). The rifamycin blood level was determined during the fever stability and changes of kinetics of the antibiotic were investigated. It was found that distribution and elimination of rifamycin were decreased during fever. The consequence of the inhibition of the antibiotic elimination was the increase of its level in blood and tissue compartments.

Animals↗

[Studies on the pharmacological bases of fetal toxicity of drugs. (I). Relation of fetal toxicity and tissue concentration of acetylsalicylic acid with pyrogen in pregnant rats].

The mechanism for the enhancing effect of pyrogen (lipopolysaccharide, LPS) on the fetal toxicity of acetylsalicylic acid (ASA) was studied in pregnant rats. The lethality of ASA was significantly enhanced by LPS in male rats. The fetal toxicity of ASA including fetal death, resorption, growth retardation, and skeletal anomalies (wavy rib and asymmetry of sternebra) was slightly observed in the dams that received a single dose of ASA (125 to 500 mg/kg, p.o.) on the 15th day of gestation, but it was markedly increased by LPS (20 micrograms/kg, i.v.). The enhancement of the toxicity of ASA by LPS was also observed in the maternal body weight gain until term. The plasma concentrations of ASA and salicylic acid (SA), the major metabolite of ASA, were increased by LPS. The tissue concentrations of SA were also increased in the following order: placenta, brain, fetus, uterus, liver and kidney. The ATP levels of placenta and fetus were not influenced by ASA alone, but markedly decreased by both LPS and ASA.

Abnormalities, Drug-Induced↗

[Hemopoietic action of the high-molecular fraction of leukocytic pyrogen].

During fractionation of the rabbit leukocytic pyrogen (LP) on Sephadex column and by the ethanol method, the apyrogenic protein fraction was isolated. In intact rats this fraction induced granulocytopoiesis stimulation: a rise in granulocyte proliferative activity, an increase in total granulocyte count in the bone marrow and peripheral blood, and also a rise in the number of macrocolonies in the spleen of lethally irradiated mice due to an increase in granulocyte colonies.

Animals↗

[Analysis of the depression of the mitotic activity of the corneal epithelium in white rats under chronic pyrogenal stress].

It was established previously that stable depression of cell division in corneal epithelium under chronic stress is not related to variations in the index of labeled nucleus (ILN). The paper demonstrates that five-day long pyrogenal injection did not alter the daily ILN: it was 67% in control rats and 69.7% in the experimental group. Cytophotometric logical sections showed that chronic stress led to a significant increase in the number of tetraploid nuclei (from 3.2 to 7.7%). No material changes were observed in the content of nuclei belonging to other classes. No polyploidization or G(2) growth evidence were recorded either. The absence of progressive rise in tetraploid nuclei and of more pronounced polyploidization in the presence of long-term depression of the cell cycle and stable ILN is explained by circadian variations in the mitotic activity reaction to stress. During chronic stress the depression of the cell cycle observed in the day and evening time was not recorded in the morning hours at the height of the mitotic activity. This circadian shunt is conducive to maintaining modal ploidity of corneal nuclei.

Animals↗

Studies on antilipolytic activity of antipyretics. Part I. Influence of sodium salicylate, acetylsalicylic acid, phenazone, aminophenazone, and acetophenidin on lipolysis in fever induced by E. coli pyrogen.

The fever induced by E. coli pyrogen (LPS) is accompanied by a rise of FFA and glycerol level. All tested antipyretics inhibited both thermogenesis of lipolysis produced by LPS. These results suggest that the antipyretic effect of antipyretic drugs is not confined to their action on heat-dissipating mechanisms, but may also be exerted by a depression of lipid metabolism.

Aminopyrine↗

Protein concentration in immunological preparations and pyrogenic reaction of rabbits.

The drop of arterial pressure was found to be caused by proteins injected intravenously into test animals. The drop was related to the protein concentration and the volume of the dose. Low pressure was caused neither by the histamine nor by the protein characterized by its property of liberating histamine. Antihistamines had no influence on quantitative or qualitative depressory reaction, caused by the presence of dissolved proteins. Concentrated protein solutions, when applied intravenously, did not contribute to identifying the pyrogenic reaction, but had a damaging effect on the organism and homeostasis of animals used in the experiments.

Animals↗